Kidney measures such as low estimated glomerular filtration rate and high albuminuria are strongly associated with mortality and end-stage renal disease across all age groups – even in the elderly, according to a collaborative meta-analysis reported online Oct. 30 in JAMA and presented simultaneously at Kidney Week.
The risk for chronic kidney disease, which in turn is closely allied with the risk for cardiovascular disease and all-cause mortality, typically is gauged by assessing estimated GFR (eGFR) and albuminuria levels. But there has been substantial controversy regarding the accuracy of these measures for predicting mortality and CKD risk in the elderly, because kidney function appears to decline markedly even in apparently healthy people as they age, said Dr. Stein I. Hallan and his associates in the Chronic Kidney Disease Prognosis Consortium.
Some experts even hold that reduced GFR might simply be part of the natural aging process and that the kidneys undergo an inevitable senescence, rendering "normal" markers of kidney function unusable in the elderly, said Dr. Hallan, of St. Olav University Hospital and the Norwegian University of Science and Technology, both in Trondheim, and his colleagues.
To examine whether aging modifies the usefulness of estimated GFR and albuminuria in assessing the risks for mortality and CKD, Dr. Hallan and his associates analyzed data from 46 different cohorts worldwide that included the entire adult age range (18-108 years). The Chronic Kidney Disease Prognosis Consortium includes data on 20 North American, 12 European, 10 Asian, 1 Australian, and 3 multinational cohorts comprising more than 2 million study subjects followed for a mean of 6 years.
Among the study cohorts, 26 involved people from the general population, 8 involved patients at high risk for vascular disease, and the remaining 12 involved patients with CKD.
During follow-up there were 112,325 deaths in the general population and the high-risk cohorts, as well as 9,037 deaths in the CKD cohorts. There were 2,766 end-stage renal disease (ESRD) events in the general population and high-risk cohorts, as well as 5,962 ESRD events in the CKD cohorts.
Both mortality risk and the risk of ESRD events strongly increased with decreasing GFR across all age groups, even though the study populations had widely divergent demographic and clinical characteristics, the investigators said. These risks declined with increasing age (JAMA 2012 Oct. 30 [doi: 10.1001/jama.2012.16817]).
This correlation remained robust when the data were adjusted to account for patient sex, race, history of cardiovascular disease, blood pressure, serum cholesterol levels, body mass index, smoking status, and diabetes status. For example, the adjusted hazard ratio for all-cause mortality in subjects with an eGFR of 45 (compared with 80) mL/min per 1.73 m2 was 3.50 in those aged 18-54 years, and declined with age to 1.35 in those aged at least 75 years.
The findings were similar for albuminuria levels, with high levels predicting mortality and ESRD events across all age groups.
"Although some variation in management of CKD should be considered by age, based on cost and benefits, with respect to risk of mortality and ESRD, our data support a common definition and staging of CKD based on eGFR and albuminuria for all age groups," they said.
These results contradict the concern "that CKD guidelines should be used with caution in older individuals and that low eGFR reflects only natural aging." They also support recommendations that CKD measures be added to mortality risk equations.
In addition, "the strong increase in mortality along with kidney measures at older ages suggests that older adults should not be left out from management strategies of CKD. Previous data show that low eGFR in the very old is associated with classical CKD complications like anemia, acidosis, hyperparathyroidism, and hyperphosphatemia," the researchers said.
This study was supported by a variety of government agencies, medical research councils, and industry sponsors. The 16 authors reported numerous ties to industry sources.